The protozoan parasite Cryptosporidium parvum is a significant cause of intractable diarrheal disease, which is refractory to a number of different modes of treatment in AIDS patients. The initial events in establishing infection by this parasite, are attachment of the sporozoite to host cells followed by invasion of the cell membrane. The molecular mechanisms underlying this initial interaction are unknown. The overall goal of our studies on cryptosporidium is to identify and characterize specific parasite and host molecules involved in attachment and invasion of Cryptosporidium. The specific aims of this proposal are directed at purifying, characterizing and cloning the gene for a sporozoite surface lectin (SSL) and determining its role in attachment and invasion and at identifying other putative attachment/invasion specific molecules. The first specific aim is to further characterize the sugar specificity of SSL, to purify the protein to homogeneity and determine amino acid sequence and to produce polyclonal and monoclonal antibodies to it. The second specific aim is to identify and characterize the host receptor for SSL. The third specific aim is to clone, sequence and analyze the gene encoding SSL. Studies undertaken as outlined in the first three specific aims will identify or produce reagents such as purified or recombinant SSL, antibodies to SSL and other putative attachment/invasion specific molecules. These reagents will then be evaluated as potential inhibitors of attachment and infection in vitro as well as in vivo in the fourth specific aim. These studies will provide a rational basis for potential treatment modalities based on inhibition of attachment and invasion of the sporozoite to host cells.